中国骨质疏松杂志

透明质酸通过TRPA1-Ca2+/ROS轴调控骨关节炎软骨稳态

Hyaluronan modulates osteoarthritis cartilage homeostasis via the TRPA1-Ca²⁺/ROS axis

DOI：10.3969/j.issn.1006-7108.2026.08.004

英文关键词:hyaluronan chondrocytes TRPA1 Ca2+ reactive oxygen species

基金项目:

作者	单位
王红1,2,3# 廖正权1,2,3,4# 岳亚茹1,2,3,5 陈文萍1,2,3*	1.南方医科大学第三附属医院,广东广州 510630 2.广东省骨科研究院,广东广州 510630 3.广东省骨科医院,广东广州 510630 4.南方医科大学第三临床医学院,广东广州 510630 5.南方医科大学第三附属医院医学影像科,广东广州 510630

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中文摘要:

目的探讨透明质酸（hyaluronan，HA）通过调控TRPA1-Ca2+/活性氧（reactive oxygen species，ROS）信号轴治疗骨关节炎（osteoarthritis，OA）的新机制。方法 18只雄性小鼠通过膝关节半月板失稳定手术（destabilization of medial meniscus，DMM）OA造模后随机分为假手术组（SHAM组）、模型组（OA组）和透明质酸组（HA组）。透明质酸组每周1次关节腔注射HA，连续4周。通过电子Von Frey检测小鼠足底疼痛阈值、番红固绿染色观察膝关节软骨组织病理变化、免疫组化染色观察膝关节软骨组织COL2、MMP13、MMP3、IL-1β、IL-6指标。在体外实验中，将小鼠原代软骨细胞使用IL-1β进行关节炎造模，后使用HA（1 mg/mL）、TRPA1抑制剂HC030031（1 μmol/L）处理，通过荧光标记检测细胞内Ca2+和ROS的变化，qRT-PCR检测细胞内COL2和MMP13表达情况。结果与模型组相比，透明质酸组痛阈升高，OARSI评分降低（P＜0.001）；软骨组织COL2升高，MMP13、MMP3、IL-1β、IL-6降低（P＜0.05）。将小鼠原代软骨细胞经IL-1β刺激，与模型组相比，透明质酸组软骨细胞TRPA1表达下降（P＜0.000 1），避免了胞内钙超载和ROS蓄积（P＜0.05），COL2 mRNA升高，MMP13 mRNA下降（P＜0.05）。此外，与模型组相比，使用TRPA1抑制剂可模拟HA作用。结论 HA可能通过抑制TRPA1通道活性减轻胞内钙超载和ROS蓄积，从而缓解疼痛和延缓软骨退变。

英文摘要:

Objective This study elucidates the novel mechanism by which hyaluronan (HA) treats osteoarthritis (OA) through regulating the TRPA1-Ca2?/ROS signaling axis. Methods Eighteen male mice were subjected to Destabilization of the Medial Meniscus (DMM) surgery to establish an OA model. The mice were then randomly divided into sham surgery (SHAM), model (OA), and hyaluronan (HA) groups. Mice in the HA group received intra-articular injections of HA once a week for 4 consecutive weeks. Mouse paw pain thresholds were assessed using electronic von Frey testing. Pathological changes in the knee cartilage tissue were observed with Safranin O-Fast Green staining. Immunohistochemical staining was used to examine COL2, MMP13, MMP3, IL-1β, and IL-6 markers in the knee cartilage tissue. In vitro experiments involved primary mouse chondrocytes treated with IL-1β to induce arthritis, followed by treatment with HA (1 mg/mL) and TRPA1 inhibitor HC030031 (1 μmol/L). Changes in intracellular Ca2+ and ROS levels were detected using fluorescence labeling. COL2 and MMP13 mRNA expressions were analyzed using qRT-PCR. Results Compared with the model group, the HA group showed an increased pain threshold and a decreased OARSI score (P< 0.001). COL2 in cartilage tissue was up-regulated and MMP13, MMP3, IL-1β, and IL-6 were down-regulated (P<0.05). In primary mouse chondrocytes stimulated with IL-1β, the HA group showed decreased TRPA1 expression compared to the model group (P<0.000 1). This reduction prevented intracellular calcium overload and ROS accumulation (P<0.05), increased COL2 mRNA levels, and decreased MMP13 mRNA levels (P<0.05). Furthermore, using a TRPA1 inhibitor could mimic the effects of HA, compared with the model group. Conclusion HA might help to ease pain and to slow down cartilage breakdown by blocking TRPA1 channels, which helps lower calcium overload and ROS buildup.

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